Development of Multifunctional Resins for Robust Dentin Bonding Project Summary The current dental restorations suffer from reduced longevity mainly due to interfacial breakdown/failures, which cause microleakage, sensitivity, recurrent caries, restoration removal/replacement and extensive loss of sound tooth structure. The breakdown has been linked to the failure of current bonding systems to develop a durable seal to dentin. Current dentin bonding strategies mainly rely on micromechanical retention between infiltrated resin and exposed collagen fibrils in the demineralized dentin layer. Strength of this interlocking or entanglement depends on the quality and longevity of both the infiltrated resin and collagen fibrils within the hybrid layer. There is substantial evidence to suggest that the quality of this layer is very poor, and the micromechanical binding mechanism is intrinsically problematic, does not provide a strong, tight, and durable seal between restorative material and dentin. Results from both in vitro and in vivo studies including ours have indicated that the following critical issues inhibit the formation of a durable bond when using current restorative bonding systems. These issues include poor/no interactions/bindings between infiltrated resin and collagen, poor quality of infiltrated resin (due to inadequate monomer/polymer conversion and hydrolysis), and degradation of acid-etched/unprotected collagen fibrils. The unprotected collagen undergoes degradation by exogenous bacteria and endogenous MMPs (which are activated immediately by acid etching), proceeding with hydrolysis of poor quality resins. It is nearly impossible to obtain strong and durable interface bonding without dramatic alterations in chemistry and/or bonding strategies. Clearly new chemistry and new bonding concept must be developed before a revolutionary improvement in dental restorations can be accomplished. In this application, we propose to develop novel monomers for robust, durable binding to address all the above issues. Such functional monomers will be designed to crosslink resin at one end and crosslink collagen fibrils at the other, not only stabilizing and increasing the longevity of both resin and collagen phases but also creating a tight, strong bond between resin polymer and dentin collagen. The approach is innovative since it represents the first systematic design with rationally engineered chemistry to simultaneously tackle all the three critical challenges afflicting current bonding systems. The overall hypothesis of this proposal is that new restorative resins formulated to induce collagen crosslinking, strong resin-collagen interactions and resin crosslinking will provide enhanced interfacial structural integrity and increased durability in the presence of clinically relevant dentin substrates. A combinatory approach/strategy together with in situ interfacial multi-scale characterization will be used in the studies. This approach will allow us to identify the most promising structures for the development of a biodegradation-resistant restorative resin that provides a durable, structurally integrated interfacial layer with clinically relevant dentin substrates.